Islet Transplantation Technology
Worldwide, 3 million patients suffer with Type 1 diabetes (these patients are unable to produce sufficient levels of insulin due to a defective pancreas) and 50 million patients have Type 2 diabetes (these patients are unable to effectively utilize insulin). The total economic burden in the US has been estimated to be almost $100 billion. Today, transplantation of donated human islets has been shown to be technically feasible. The Edmonton protocol (Shapiro et al.) demonstrated that patients with Type 1 diabetes and a history of severe hypoglycemia can become insulin-free through islet cell transplantation. Islet cells isolated from harvested cadaver pancreases are injected into the portal vein of the liver. This procedure, which has been implemented at a number of clinical centers worldwide, including at the University of Pittsburgh Medical Center, offers the opportunity to forever change the field of diabetes treatment. However, it suffers from the same problem affecting whole organ transplant: a limited supply of donor material. The protocol requires 600,000 functional islets, the equivalent of two donor organs after islet isolation. As human pancreases are in very short supply, fewer than 100 islet transplants are performed per year, thus there is clearly a huge unmet clinical need in sourcing islets or insulin-producing cells.
What about stem cells for diabetes therapy? Efforts to produce a fully-functional, human insulin-producing cell have met with little success. We estimate that pig-islet R&D has a 10 year lead on the stem cell field. While stem-cell-derived insulin-producing cells have been isolated, they are impure, with the added risk that teratomas could arise from residual contaminating stem cells. However, in the long term future, it is possible that functional islet cells could be produced from stem cells. It should be noted that patients receiving such stem-cell derived transplants will still require immunosuppression—to prevent recurrence of disease (especially Type1 Diabetes) in the transplanted stem cell. Efforts to produce an “artificial islet” –by transferring critical genes to cells which have machinery capable of making insulin, e.g. liver cells, have failed since the engineered cells are not responsive to glucose. Pig islets make insulin (pig insulin has been used in humans for more than 60 years), and through genetic modification, can resist rejection, so that they function equivalently to human islets, and importantly, their supply can be readily scaled up in environmentally-controlled housing to meet patient need.
The field of diabetes therapeutics is obviously quite competitive, primarily due to the large patient population, unmet clinical need, and sizable market potential. Revivicor’s porcine-derived genetically modified islet cells provide a number of advantages over existing technologies and therapies. Unlike insulin therapy, which has a number of serious side effects, and is difficult to regulate, whole islets or insulin-producing cells offer natural, glucose-responsive, endogenous control of insulin levels. Because these cells have been modified to inhibit rejection, they can be maintained in the body without encapsulation, using protocols similar to those developed by the Edmonton group for human islets. The pig source of islets is unlimited, fully scalable in specific-pathogen-free (SPF) pig facilities, and thus would be amenable to large scale, FDA-regulated manufacturing practices.
Recent Islet Research Success At Revivicor
In December 2009, results were published in the American Journal of Transplantation, obtained through Revivicor’s ongoing collaboration with Dr. Massimo Trucco and David Cooper (Children’s Hospital/University of Pittsburgh); 5 diabetic monkeys were transplanted with islets from Revivicor genetically modified pigs. Immediate and complete reversal of diabetes was demonstrated (complete cure from day 1 post-transplant), without the need for insulin injections and continuing for 3 months up to >12 months; these are the best results ever observed in the field. These results have shown the potential that genetically modified pig islets can provide in treatment and cure of this intractable disease.
News Articles Detailing This Breakthrough
The Pittsburgh Post-Gazette, December 4, 2009
The Roanoke Times, January 2, 2010
GE pig islets, for over one year in monkeys, normalize blood gluclose (BG) levels with no need for insulin.
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